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Sci Rep. 2015 Nov 4;5:16127. doi: 10.1038/srep16127.

Effects and possible mechanisms of action of acacetin on the behavior and eye morphology of Drosophila models of Alzheimer's disease.

Author information

1
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.
2
Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
3
R&D Coordination Division, Rural Development Administration, Jeonju 560-500, Republic of Korea.
4
College of Plant Science &Technology, Huazhong Agricultural University, Wuhan 430070, Hubei, P.R. China.

Abstract

The human β-amyloid (Aβ) cleaving enzyme (BACE-1) is a target for Alzheimer's disease (AD) treatments. This study was conducted to determine if acacetin extracted from the whole Agastache rugosa plant had anti-BACE-1 and behavioral activities in Drosophila melanogaster AD models and to determine acacetin's mechanism of action. Acacetin (100, 300, and 500 μM) rescued amyloid precursor protein (APP)/BACE1-expressing flies and kept them from developing both eye morphology (dark deposits, ommatidial collapse and fusion, and the absence of ommatidial bristles) and behavioral (motor abnormalities) defects. The reverse transcription polymerase chain reaction analysis revealed that acacetin reduced both the human APP and BACE-1 mRNA levels in the transgenic flies, suggesting that it plays an important role in the transcriptional regulation of human BACE-1 and APP. Western blot analysis revealed that acacetin reduced Aβ production by interfering with BACE-1 activity and APP synthesis, resulting in a decrease in the levels of the APP carboxy-terminal fragments and the APP intracellular domain. Therefore, the protective effect of acacetin on Aβ production is mediated by transcriptional regulation of BACE-1 and APP, resulting in decreased APP protein expression and BACE-1 activity. Acacetin also inhibited APP synthesis, resulting in a decrease in the number of amyloid plaques.

PMID:
26530776
PMCID:
PMC4632086
DOI:
10.1038/srep16127
[Indexed for MEDLINE]
Free PMC Article

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